Fusion molecules and IL-15 variants

Abstract

The instant invention provides soluble fusion protein complexes and IL-15 variants that have therapeutic and diagnostic use, and methods for making the proteins. The instant invention additionally provides methods of stimulating or suppressing immune responses in a mammal using the fusion protein complexes and IL-15 variants of the invention.

What is claimed is: 
     
       1. A soluble fusion protein complex comprising at least two soluble fusion proteins, wherein:
 the first fusion protein comprises (a) a first antibody covalently linked to (b) human interleukin-15 (N72D) (huIL-15(N72D)) polypeptide; and 
 the second fusion protein comprises (c) interleukin-15 receptor alpha (IL-15Rα) polypeptide; 
 wherein the huIL-15(N72D) polypeptide of the first fusion protein is bound to the IL-15Rα polypeptide of the second fusion protein to form a soluble fusion protein complex. 
 
     
     
       2. The soluble fusion protein complex of  claim 1 , wherein one or both of the first and second fusion proteins further comprise an immunoglobulin Fc domain. 
     
     
       3. The soluble fusion protein complex of  claim 2 , wherein the second fusion protein comprises an antibody covalently linked to the IL-15Rα polypeptide. 
     
     
       4. The soluble fusion protein complex of  claim 2 , wherein the antibody is a single-chain antibody or single-chain Fv. 
     
     
       5. A soluble fusion protein complex comprising at least two soluble fusion proteins, wherein:
 the first fusion protein comprises (a) a human IL-15(N72D) polypeptide; and 
 the second fusion protein comprises (b) an antibody covalently linked to (c) an IL-15Rα polypeptide; 
 wherein the human IL-15(N72D) polypeptide of the first fusion protein is bound to the IL-15Rα polypeptide of the second fusion protein to form a soluble fusion protein complex. 
 
     
     
       6. The soluble fusion protein complex of  claim 5 , wherein one or both of the first and second fusion proteins further comprise an immunoglobulin Fc domain. 
     
     
       7. The soluble fusion protein complex of  claim 6 , wherein the antibody is a single-chain antibody or single-chain Fv.